Method of treating gastrointestinal disorders, particularly colitis

Abstract

Administration of alkoxylated acyl glycerine (AAG) containing lower carboxylic acid acyl moieties to mammalian subjects results in increase of lower carboxylate concentration, particularly in the colon, and may be used to treat such disorders as simple colitis, ulcerative colitis, divertive colitis, colorectal cancer, and other diseases of the gastrointestinal tract where lower carboxylates are implicated. The AAG encourage patient compliance due to substantially no odor, even when butyric acid acyl groups are employed.

What is claimed is:  
     
       1. An alkoxylated acyl glycerol (AAG) useful for administration to mammalian subjects having a need for increased gastrointestinal lower carboxylate, comprising a compound of the formula                    
       wherein each n individually is an integer from 1 to 5, 
       R is                    
       wherein x is an integer from 0 to 2, wherein R 2  and R 3  individually are H or C 1-4  lower alkyl, wherein R 1  is H or C 2-6  lower alkyl; one or two of R 1  may be a C 7-24  alkyl or alkenyl group; with the proviso that at least one R 1  is C 2-6  lower alkyl, the compounds are absorbable and/or digestible in the gastrointestinal tract or associated organs to liberate free carboxylic acid of the formula                    
       where R 4  is C 2-6  lower alkyl. 
     
     
       2. The AAG of  claim 1 , wherein one of R 2  and R 3  is —CH 3  and the other of R 2 and R 3  is H. 
     
     
       3. The AAG of  claim 1  wherein on average the total of all n is from 2 to 5. 
     
     
       4. The AAG of  claim 1 , wherein not more than 1.5 groups (RO) on average contain R other than 2-methylethylene or 1-methylethylene. 
     
     
       5. The AAG of  claim 1 , wherein at least 2 of R 1  on average are n-C 3  alkyl groups. 
     
     
       6. The AAG of  claim 1 , wherein from 0.5 o 1.5 of R 1  on average are C 11-23  alkyl groups or C 11-23  alkenyl groups. 
     
     
       7. The AAG of  claim 1 , wherein all —(RO)— are derived from propylene oxide, the sum of all n ranges from 1.5 to 4, and R 1  is n-C 3  alkyl. 
     
     
       8. A process for increasing the lower carboxylate content of the gastrointestinal tract of a mammal, comprising administering a lower carboxylate-increasing amount of an alkoxylated acyl glycerol (AAG) comprising:                    
       wherein each n individually is an integer from 1 to 5, 
       R is                    
       wherein x is an integer from 0 to 2, wherein R 1  and R 3  individually are H or C 1-4  lower alkyl, wherein R 1  is H or C 1-6  lower alkyl; one or two of R 1  may be a C 7-24  alkyl or alkenyl group; with the proviso that at least one R 1  is C 1-4  lower alkyl, the compounds are absorbable and/or digestible in the gastrointestinal tract or associated organs to liberate free carboxylic acid of the formula                    
       where R 4  is C 1-6  lower alkyl. 
     
     
       9. A process for increasing the lower carboxylate content of the gastrointestinal tract of a mammal, comprising administering a lower carboxylate-increasing amount of the AAG of  claim 8  wherein one of R 2  and R 3  is —CH 3  and the other of R 2  and R 3  is H. 
     
     
       10. A process for increasing the lower carboxylate content of the gastrointestinal tract of a mammal, comprising administering a lower carboxylate-increasing amount of the AAG of  claim 8  wherein at least two of R 1  on average are n-C 3  alkyl groups. 
     
     
       11. A process for increasing the lower carboxylate content of the gastrointestinal tract of a mammal, comprising administering a lower carboxylate-increasing amount of the AAG of  claim 8  wherein all —(RO)— are derived from propylene oxide, the sum of all n on average ranges from 1.5 to 4, and R 1  is n-C 3  alkyl. 
     
     
       12. The process of  claim 8  wherein the lower carboxylate content in the colon is increased. 
     
     
       13. A method of ameliorating a medical disorder caused by low lower carboxylate availability in the gastrointestinal tract or associated organs or treatable by raising concentration of lower carboxylate in the lower gastrointestinal tract or associated organs, said method comprising administration to a patient exhibiting symptoms of said medical disorder a lower carboxylate increasing amount of an alkoxylated acyl glycerol AAG having the formula:                    
       wherein each n individually is an integer from 1 to 5, 
       R is                    
       wherein x is an integer from 0 to 2, wherein R 2  and R 3  individually are H or C 1-4  lower alkyl, wherein R 1  is H or C 1-6  lower alkyl; one or two of R 1  may be a C 7-24  alkyl or alkenyl group; with the proviso that at least one R 1  is C 1-6  lower alkyl, the compounds are absorbable and/or digestible in the gastrointestinal tract or associated organs to liberate free carboxylic acid of the formula                    
       where R 4  is C 1-6  lower alkyl. 
     
     
       14. A method of ameliorating a medical disorder caused by low lower carboxylate availability in the gastrointestinal tract or associated organs or treatable by raising concentration of lower carboxylate in the lower gastrointestinal tract or associated organs, said method comprising administration to a patient exhibiting symptoms of said medical disorder a lower carboxylate increasing amount of the AAG of  claim 13 , wherein one of R 2  and R 3  is H and the other of R 2  and R 3  is CH 3 . 
     
     
       15. A method of ameliorating a medical disorder caused by low lower carboxylate availability in the gastrointestinal tract or associated organs or treatable by raising concentration of lower carboxylate in the lower gastrointestinal tract or associated organs, said method comprising administration to a patient exhibiting symptoms of said medical disorder a lower carboxylate increasing amount of the AAG of  claim 13 , wherein at least two of R 1  on average are n-C 3  alkyl groups. 
     
     
       16. A method of ameliorating a medical disorder caused by low lower carboxylate availability in the gastrointestinal tract or associated organs or treatable by raising concentration of lower carboxylate in the lower gastrointestinal tract or associated organs, said method comprising administration to a patient exhibiting symptoms of said medical disorder a lower carboxylate increasing amount of the PAG of  claim 13 , wherein all —(RO)— are derived from propylene oxide, the sum of all n on average ranges from 1.5 to 4, and R 1  is n-C 3  alkyl. 
     
     
       17. The method of  claim 13 , wherein 5-aminosalicylic acid and/or one or more corticosteroids are administered concurrently. 
     
     
       18. A method of prophylactsis of the gastrointestinal tract of a mammal against gastrointestinal disorders, comprising administering to said mammal a prophylactic amount of an alkoxylated acyl glycerol (AAG) having the formula:                    
       wherein each n individually is an integer from 1 to 5, 
       R is                    
       wherein x is an integer from 0 to 2, wherein R 2  and R 3  individually are H or C 1-4  lower alkyl, wherein R 1  is H or C 1-6  lower alkyl; one or two of R 1  may be a C 7-24  alkyl or alkenyl group; with the proviso that at least one R 1  is C 1-6  lower alkyl, the compounds are absorbable and/or digestible in the gastrointestinal tract or associated organs to liberate free carboxylic acid of the formula                    
       where R 4  is C 1-6  lower alkyl. 
     
     
       19. The method of  claim 18  wherein all —(RO)— are derived from propylene oxide. 
     
     
       20. The method of  claim 18  wherein at least two of R 1  are n-C 3 .